1-182582202-A-T

Variant names:

• chr1-182582202-A-T
• rs627928
• NM_021133.4:c.1623T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021133.4(RNASEL):​c.1623T>A​(p.Asp541Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RNASEL NM_021133.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 0 publications found

Genes affected

RNASEL (HGNC:10050): (ribonuclease L) This gene encodes a component of the interferon-regulated 2-5A system that functions in the antiviral and antiproliferative roles of interferons. The protein is involved in innate immunity and is active against multiple RNA viruses, including the influenza and SARS-CoV-2 viruses. Mutations in this gene have been associated with predisposition to prostate cancer and this gene is a candidate for the hereditary prostate cancer 1 (HPC1) allele. [provided by RefSeq, Nov 2021]

RNASEL Gene-Disease associations (from GenCC):

• prostate cancer, hereditary, 1

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.024449706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASEL	NM_021133.4	c.1623T>A	p.Asp541Glu	missense_variant	Exon 4 of 7	ENST00000367559.7	NP_066956.1
RNASEL	XM_047427096.1	c.1623T>A	p.Asp541Glu	missense_variant	Exon 4 of 7		XP_047283052.1
RNASEL	XM_047427106.1	c.1623T>A	p.Asp541Glu	missense_variant	Exon 4 of 6		XP_047283062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASEL	ENST00000367559.7	c.1623T>A	p.Asp541Glu	missense_variant	Exon 4 of 7	1	NM_021133.4	ENSP00000356530.3
RNASEL	ENST00000539397.1	c.1623T>A	p.Asp541Glu	missense_variant	Exon 4 of 6	2		ENSP00000440844.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 61

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.0090
DANN	Benign	0.18
DEOGEN2	Benign	0.028	T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Benign	0.052	T;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.024	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.41	N;N
PhyloP100		-2.3
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.86	N;N
REVEL	Benign	0.012
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.015
MutPred		0.14		Loss of ubiquitination at K543 (P = 0.1037);Loss of ubiquitination at K543 (P = 0.1037);
MVP		0.29
MPC		0.051
ClinPred		0.017	T
GERP RS		-5.6
Varity_R		0.065
gMVP		0.082
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs627928; hg19: chr1-182551337;